Background and Aims: A significant number of postmenopausal women have both diabetes and osteoporosis in our country. The objectives of the study were to study the effect of intravenous (IV) zolendronic acid (ZA) on change in bone mineral density (BMD) at lumbar spine (LS), total hip (TH), femoral neck (FN) and distal forearm (FA) and the changes in bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes after 12 months of treatment.Results: A total of 80 patients with postmenopausal osteoporosis were included-diabetes (n=40) and non-diabetes (n=40). Patients with diabetes were older and had lower BTMs levels compared to non-diabetic patients. At baseline, BMD at all four areas were similar in both the groups. Mean increase in LS-BMD at 12-months in diabetes and non-diabetes group was 3.6 ± 4.7% and 6.2 ± 4.7 % respectively (P=0.02). There was no difference in the percent change in the TH, FN and FA BMD between the groups at 12 months. There was a significant reduction in BTMs from the baseline in both the groups after 12 months of follow-up. Acute phase reactions were seen in 75% of patients with pyrexia being more common in non-diabetes group.Conclusion: The gain in the LS-BMD was significantly lower in the diabetes group as compared to the non-diabetes group at 12 months following a single IV infusion of 4 mg ZA.